De Vivo Immaculata, Hankinson Susan E, Colditz Graham A, Hunter David J
Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Breast Cancer Res. 2004;6(6):R636-9. doi: 10.1186/bcr928. Epub 2004 Sep 22.
Recent evidence suggests a role for progesterone in breast cancer development and tumorigenesis. Progesterone exerts its effect on target cells by interacting with its receptor; thus, genetic variations, which might cause alterations in the biological function in the progesterone receptor (PGR), can potentially contribute to an individual's susceptibility to breast cancer. It has been reported that the PROGINS allele, which is in complete linkage disequilibrium with a missense substitution in exon 4 (G/T, valine-->leucine, at codon 660), is associated with a decreased risk for breast cancer.
Using a nested case-control study design within the Nurses' Health Study cohort, we genotyped 1252 cases and 1660 matched controls with the use of the Taqman assay.
We did not observe any association of breast cancer risk with carrying the G/T (Val660-->Leu) polymorphism (odds ratio 1.10, 95% confidence interval 0.93-1.30). In addition, we did not observe an interaction between this allele and menopausal status and family history of breast cancer as reported previously.
Overall, our study does not support an association between the Val660-->Leu PROGINS polymorphism and breast cancer risk.
近期证据表明孕酮在乳腺癌发展和肿瘤发生中起作用。孕酮通过与其受体相互作用对靶细胞发挥作用；因此，可能导致孕酮受体（PGR）生物学功能改变的基因变异可能会增加个体患乳腺癌的易感性。据报道，PROGINS等位基因与外显子4中的错义替换（G/T，缬氨酸→亮氨酸，密码子660）完全连锁不平衡，与乳腺癌风险降低相关。
在护士健康研究队列中采用巢式病例对照研究设计，我们使用Taqman分析对1252例病例和1660例匹配对照进行基因分型。
我们未观察到携带G/T（Val660→Leu）多态性与乳腺癌风险之间存在任何关联（比值比1.10，95%置信区间0.93 - 1.30）。此外，我们也未观察到该等位基因与绝经状态以及既往报道的乳腺癌家族史之间存在相互作用。
总体而言，我们的研究不支持Val660→Leu PROGINS多态性与乳腺癌风险之间存在关联。
